PDBsum entry 1nsg

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Complex (isomerase/kinase) PDB id
Protein chains
107 a.a. *
94 a.a. *
Waters ×126
* Residue conservation analysis
PDB id:
Name: Complex (isomerase/kinase)
Title: The structure of the immunophilin-immunosuppressant fkbp12-r complex interacting with human frap
Structure: Fk506-binding protein. Chain: a. Synonym: fkbp-12. Engineered: yes. Fkbp-rapamycin associated protein (frap). Chain: b. Synonym: frap. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Gene: human hippocampal cdna library. Expressed in: escherichia coli. Expression_system_taxid: 562. Palo alto, ca). Palo alto, ca)
2.20Å     R-factor:   0.196     R-free:   0.265
Authors: J.Liang,J.Choi,J.Clardy
Key ref:
J.Liang et al. (1999). Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr, 55, 736-744. PubMed id: 10089303 DOI: 10.1107/S0907444998014747
01-Jul-97     Release date:   18-Mar-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P62942  (FKB1A_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP1A
108 a.a.
107 a.a.
Protein chain
Pfam   ArchSchema ?
P42345  (MTOR_HUMAN) -  Serine/threonine-protein kinase mTOR
2549 a.a.
94 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 2: Chain A: E.C.  - Peptidylprolyl isomerase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Peptidylproline (omega=180) = peptidylproline (omega=0)
Peptidylproline (omega=180)
= peptidylproline (omega=0)
   Enzyme class 3: Chain B: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   10 terms 
  Biological process     chaperone-mediated protein folding   33 terms 
  Biochemical function     ion channel binding     16 terms  


DOI no: 10.1107/S0907444998014747 Acta Crystallogr D Biol Crystallogr 55:736-744 (1999)
PubMed id: 10089303  
Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.
J.Liang, J.Choi, J.Clardy.
The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12-rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar to that observed in the FKBP12-rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.
  Selected figure(s)  
Figure 1.
Figure 1 Chemical structures of (a) FK506 and (b) rapamycin, showing the regions interacting with FKBP12 and FRB or calcineurin (effector region).
Figure 2.
Figure 2 Stereoviews of (a) the rapamycin-binding pocket of FRB and (b) the rapamycin-binding pocket of FKBP12. Hydrogen bonds between rapamycin and FKBP12 are indicated by dashed lines, the ligand is in bold lines and the protein has light lines and residue labels.
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 736-744) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference Google scholar

  PubMed id Reference
20863387 C.A.Shertz, R.J.Bastidas, W.Li, J.Heitman, and M.E.Cardenas (2010).
Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom.
  BMC Genomics, 11, 510.  
19296866 L.N.Johnson (2009).
Protein kinase inhibitors: contributions from structure to clinical compounds.
  Q Rev Biophys, 42, 1.  
14576331 N.Jullien, F.Sampieri, A.Enjalbert, and J.P.Herman (2003).
Regulation of Cre recombinase by ligand-induced complementation of inactive fragments.
  Nucleic Acids Res, 31, e131.  
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